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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Perez, C. F. Roninson, I. B. Stern, R. K. Choi, K. Kriegler, M. Tsuruo, T. Frommel, T. O. |
| Description | Author Affiliation: Choi K ( Department of Genetics, University of Illinois, Chicago 60612.); |
| Abstract | Multidrug resistance (MDR) in mammalian cells is associated with the expression of the MDR1 gene encoding P-glycoprotein (P-gp), an and active efflux pump for various lipophilic compounds. MDR transfectants can be isolated after MDR1 gene transfer and selection with cytotoxic drugs; low levels of drug resistance have also been observed in unselected NIH 3T3 mouse cells after retrovirus-mediated transfer of mouse mdr1 cDNA. MDR cell lines possess multiple phenotypic changes, suggesting that P-gp function could be complemented by some additional mechanisms associated with cytotoxic selection. To determine whether cytotoxic selection contributes to the MDR phenotype of MDR1-expressing cells, NIH 3T3 cells infected with a recombinant retrovirus carrying the human MDR1 gene were selected by two different procedures: (i) noncytotoxic selection for increased P-gp expression on the cell surface by multiple rounds of immunofluorescence labeling and flow sorting or (ii) one or more steps of selection with a cytotoxic drug. The levels of MDR in both types of infectants showed an excellent correlation with the P-gp density in the plasma membrane, expressed as immunoreactivity with a P-gp-specific antibody normalized by reactivity with an antibody against an unrelated antigen. Cytotoxic selection conferred no additional increase in resistance relative to P-gp density. These results indicate that P-gp density in the plasma membrane may be sufficient to determine the level of MDR. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 16 |
| Volume Number | 88 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1991-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Drug Resistance Genetics Membrane Glycoproteins Transfection Vinblastine Pharmacology Animals Blotting, Southern Cell Line Cell Membrane Physiology Cell Survival Drug Effects Fluorescent Antibody Technique Metabolism Mice P-Glycoprotein RNA, Messenger Retroviridae Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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